Is DTX2 p.Ala17Val (c.50C>T) pathogenic?

DTX2 p.Ala17Val (c.50C>T) is classified Likely benign in DTX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-28). AlphaMissense: likely benign (0.0547); Very rare (popmax 0.00203%, nfe).

How common is DTX2 p.Ala17Val (c.50C>T) in the general population?

DTX2 p.Ala17Val (c.50C>T) is very rare (popmax 0.00203%, nfe) (gnomAD).

What do computational predictors say about DTX2 p.Ala17Val (c.50C>T)?

AlphaMissense predicts likely benign (score 0.0547) — an in-silico prediction, not a clinical call.

DTX2 p.Ala17Val

c.50C>T · VCV3842790

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0547 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0547	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -6.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.57, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 2,592 bp · p 1.6e-06 · regional, not allelic
Overall
CADD	14.22	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,179,946 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00167% 27/1,612,282 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00203%	49,164
Admixed American	0.00167%	59,992
Remaining individualsnot grpmax-eligible	0.0016%	62,342
African / African-American	0.00134%	74,882

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DTX2
Protein: p.Ala17Val
Coding: c.50C>T
MANE Select: NM_001102594
Type: single nucleotide variant
Location: chr7:76480559 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.01 · 4 PDB
Residue 17: the wwe 1 domain

Full DTX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTX2 p.Ala17Thr Uncertain significance ★ ⚠ same residue
DTX2 p.Ala422= Likely benign ★★ same type
DTX2 p.Gly515= Likely benign ★★ same type
DTX2 p.Pro484= Benign ★★ same type
DTX2 p.Ala146Asp Uncertain significance ★ ⚠ same type
DTX2 p.Ala187Ser Uncertain significance ★ ⚠ same type
DTX2 p.Ala195Ser Uncertain significance ★ ⚠ same type
DTX2 p.Ala255Gly Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dtx2-p-ala17val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown